IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

TY - JOUR

T1 - IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

AU - Skov, L.

AU - Beurskens, F.J.

AU - Reitamo, S.

AU - Teeling, J.

AU - Satijn, D.

AU - Knudsen, K.M.

AU - Boot, E.P.J.

AU - Hudson, D.

AU - Baadsgaard, O.

AU - Parren, P.W.H.I.

AU - Winkel, J.G.J.V. de

AU - Zachariae, Claus

N1 - Times Cited: 0ArticleEnglishParren, P. W. H. IGenmab BV, Yalelaan 60, NL-3584 CM Utrecht, NetherlandsCited References Count: 46322WBAMER ASSOC IMMUNOLOGISTS9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USABETHESDA

PY - 2008

Y1 - 2008

N2 - IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a >= 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction Udgivelsesdato: 2008/7/1

AB - IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a >= 50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction Udgivelsesdato: 2008/7/1

M3 - Journal article

SN - 0022-1767

VL - 181

SP - 669

EP - 679

JO - Journal of Immunology

JF - Journal of Immunology

IS - 1

ER -